Environmental Neurotoxins and Parkinson’s Disease – The α-Synuclein Connection and the Connection to the Florida Citrus Industry
Research Laboratory of Dr. Pedro Fernandez Fuentes, Department of Neurology
Parkinson’s disease (PD) is the most common movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of proteinaceous aggregates enriched in α-Synuclein (α-Syn) called Lewy bodies. Most PD cases have a sporadic origin; however, recent studies have shown that environmental toxins, including pesticides, induce α-Syn aggregation and may cause PD symptoms. For instance, paraquat and rotenone induce α-Syn up-regulation and aggregation, and elicit loss of dopaminergic neurons in mice and rats, respectively.
The fact that there is a high incidence of PD in rural areas made us wonder whether other pesticides commonly used in farming and in the Florida Citrus Industry also had the ability to induce α-Syn aggregation. A graduate student in our laboratory (Giridhar Murlidharan) developed a cellular assay to identify pesticides that induce α-Syn aggregation. He treated differentiated human neuroblastoma SY5Y cells expressing a α-Syn-GFP fusion with the 21 most commonly used pesticides in Florida’s orange industry for 24 hrs. Then, he visualized the α-Syn aggregation in fixed cells under the microscope. His findings revealed that three herbicides (2, 4 D-isopropylamine, norflurazon and diuron), three insecticides (diflubenzuron, pyridaben and carbaryl) and four fungicides (mefonoxam, azoxystrobin, thiabendazole and imazalil) induced α-Syn aggregation. He then combined the pesticides that did not induce α-Syn aggregation with a low dose of diuron, a potent inducer of α-Syn aggregation, and found that two more insecticides (abamectin and sulfur) and 2 herbicides (simazine and glycophosate) induced α-Syn aggregation. Also, the herbicide isopropylamine showed a distinctive change in the aggregation pattern. These findings demonstrated that 14 out of 21 pesticides used in the orange industry have the ability to induce α-Syn aggregation, thus suggesting a potential link to PD in an agricultural environment.
Understanding the risks associated with the current farming practices should contribute to reducing the incidence of sporadic PD in rural and farming environments. We are interested in exploring this research in animal models and translating discovery into preventative practices for humans.
*Work supported by the Greene Family Fund, University of Florida Foundation